Genetic Testing Considerations for Breast Cancer Patients

Genetic Testing Considerations for Breast Cancer Patients

February 26, 2020

ACMG statement upholds guidelines based on risk stratification.

There is currently insufficient evidence to support testing all patients with breast cancer for BRCA1/2 alone or in combination with other multigene panels, according to a statement released in December on behalf of the American College of Medical Genetics and Genomics (ACMG).

Published in Genetics Medicine, the ACMG document recommended that all breast cancer patients be individually evaluated to determine the need for genetic testing.

“What we are saying is that all women with breast cancer should be evaluated for the need for genetic testing based on existing clinical criteria,” said Tuya Pal, M.D., first author on the statement, Ingram Associate Professor of Cancer Research and associate director for Cancer Health Disparities at Vanderbilt-Ingram Cancer Center.

“All women with breast cancer should be evaluated for the need for genetic testing based on existing clinical criteria.”

Pal and co-authors emphasized that outcomes are not improved by testing alone but rather the subsequent implementation of appropriate care. Without the implementation of risk-adherent follow-up care, patient outcomes will not be improved, they said.

Characterizing Risk

When a pathogenic or likely pathogenic (P/LP) variant is identified, follow-up care is guided by penetrance data. For genes with high penetrance, enhanced screening or risk-reducing mastectomy (RRM) may be recommended. For moderate penetrance genes, only enhanced screening but not RRM is recommended.

But penetrance is incompletely characterized for P/LP variants in many genes on multigene panels. Additionally, for a number of genes on existing panels, breast cancer risk has yet to be established.

“We expect that the evidence to support testing may evolve at different rates for different genes,” Pal said, “And we expect that therapeutic indications will play a major role in the incorporation of genes to multigene panels.”

Concurrent Counseling

Clinical criteria to consider regarding genetic testing include age at diagnosis, family cancer history, expression of estrogen-progesterone receptors and HER2 expression, and disease stage. When patients do receive genetic testing, the statement from the ACMG underscores the importance of parallel genetic counseling.

Communicating accurate information to patients regarding their genetic testing results is important in preventing inappropriate management. As an example, while RRM is a consideration for women with a P/LP variant in BRCA1/2, high rates of bilateral mastectomy have been reported among patients with a variant of uncertain significance in BRCA1/2.

“As genetic testing now has the potential to guide cancer care, it has become imperative to ensure that all populations may benefit from these tremendous advances and that existing disparities in testing do not widen,” Pal said. “To ensure this, we need to be intentional in developing and disseminating efforts such that improved outcomes based on genetic testing are experienced across populations.”

“As genetic testing now has the potential to guide cancer care, it has become imperative to ensure that all populations may benefit from these tremendous advances and that existing disparities in testing do not widen.”